Study On Nicardipine Hydrochloride Of Controlled-Release Tablets

This paper is mainly researching on the recipe, technique, bioavailability and in vitro-in vivo correlation of insoluble nicardipine hydrochloride' s bi-layer osmotic pump tablets; a preliminary research on the recipe of the said drug' s mono-layer osmotic pump tablets has also been involved.While researching on the recipe and technique of the bi-layer osmotic pump tablets, first , we used the cumulative release amount within 12 hours and the linear release to measure the influence of the factors (core of the tablets, membrane compositions, relative techniques and in vitro-in vivo release conditions) by single-factor analysis method, and selected the dominatingly influence factors. Second, we used 3 hours, 8 hours, 12 hours cumulative release amount F3, F8, F12 as the index to screen the best recipe with multivariable linear stepwise regressing analysis. Finally , we picked out optimized prescription by 34 factors-analysis orthogonal design. We found that the bi-layer osmotic tablets cumulatively released the drug more than 80% in 12 hours, and completely released the drug within 16 hours (>90%), owning obvious zero-order release characters(r=0. 9994) within 12 hours. While the mono-layer osmotic tablets cumulative releasedonly 77. 6% in 12 hours and the utmost release amount was below 90%( not completely release), with obvious zero-order release characters.While researching on the drug' s in-vivo pharmacokinetics of the bi-layer osmotic pump tablets, we selected normal tablets as contrast preparation containing the same drug, 6 healthy dogs as test objects, to administrate in the same dose once and measured the bioavailability in vitro-in vivo correlation in plasma with HPLC. The results showed: Tmax of bi-layer osmotic tablet and normal tablet was 7.0±1.6h and 1.2±0.4h respectively; Cmax was 43. 3 ± 7. 2ng/ml and 139. 36 + 10. 5ng/ml; Tl/2 was 8.6=1.3 and 2.3 ±0.4h; Ke was 0.08 ± 0. 01h-1 and 0.3±0. 1h-1; AUC0- was 1016. 3 ± 66. 9ng. h/ml and 921. 3 ± 16. 0ng. h/ml respectively; the relative bioavailability was 110.3% with better in vitro-in vivo correlation (r=0. 9900).Conclusion: nicardipine hydrochloride bi-layer osmotic pump tablets had obvious in vitro-in vivo controlled release effect.